Solid delivery systems are useful in a wide variety of applications such as controlled release of labile molecules, particularly bioactive materials such as organic pharmaceutical compounds, enzymes, vaccines and biological control agents such as pesticides and pheromones.
Drugs and other active agents are frequently administered orally by means of solid dosage forms, such as tablets and capsules. Other oral solid dosage forms include lozenges and other hard candies. Solid dosage forms can also be implanted subcutaneously for drug delivery. Additionally, solid dosage forms are delivered intravenously, or by inhalation to the pulmonary system.
Solid dose delivery of bioactive materials to biological tissues such as mucosal, dermal, ocular, subcutaneous, intradermal and pulmonary offers several advantages over methods such as hypodermic injection and transdermal administration via so-called “patches”. Using injection, there may be physical discomfort, and there is a risk of infection using conventional needles and syringes. Many drugs are not suitable for transdermal delivery, nor have transdermal drug release rates for those capable of such delivery been perfected. Additionally, transdermal patches often cause topical reactions, in many instances precluding their long-term use.
A variety of formulations have been provided for administration in aerosolized form to mucosal surfaces, particularly “by-inhalation” (naso-pharyngeal and pulmonary). Compositions for by-inhalation administration generally comprise a liquid formulation of the pharmaceutical agent and a device for delivering the liquid formulation in aerosolized form.
U.S. Pat. No. 5,011,678 describes compositions containing a pharmaceutically active substance, a biocompatible amphiphilic steroid and a biocompatible hydrofluorocarbon propellant. U.S. Pat. No. 5,006,343 describes compositions containing liposomes, a pharmaceutically active substance and an alveolar surfactant protein that enhances transport of the liposomes across a pulmonary surface. U.S. Pat. No. 5,608,647 describes methods for administering controlled amounts of aerosol medication from a valved canister.
One drawback to the use of aerosolized formulations is that maintenance of pharmaceutical agents in aqueous suspensions or solutions can lead to lossofactivity and bioavailability. The loss of activity can be partially prevented by refrigeration, but this limits the utility of these formulations. The use of powdered formulations overcomes many of these drawbacks. The particle size of such powders is 0.5-5 μm, in order to attain deep alveolar deposition in pulmonary delivery. Unfortunately, powders of such particle size tend to absorb water and clump, thus reducing deposition of the powder in the deep alveolar spaces.
WO-A-96/03978 describes powders suitable for use in by-inhalation delivery. The powders are of uniform particle size and can be produced with varying degrees of hydrophobicity to reduce clumping and increase drug release in the surfactant environment of the lung. They may also be useful for ballistic delivery.
WO-A-96/03978 describes solid dose delivery systems which include a vitreous vehicle loaded with a guest substance, and which are capable of releasing the quest substance at a controlled rate. Controlled release is achieved by the use of glass-forming, hydrophobically derivatized carbohydrates as solid vehicles, the derivative group being selected to reduce solubility of the matrix material in aqueous media.
WO-A-99/01463 discloses polysaccharides, in which the saccharide units are linked via glycosidic bonds, and in which at least some of the OH groups are derivatised in the form of an ester or ether.
WO-A-99/33853 discloses derivatised carbohydrates, in which some OH groups are substituted with a branched hydrophobic chain, e.g. via an ester or other linkage. Such carbohydrates may be used to form solid delivery systems, e.g. incorporating a therapeutic agent, and which can be in the form of particles intended for administration by inhalation.
For drug delivery, it is advantageous if solid drug delivery systems can have defined size, shape, density and dissolution rate. It is also advantageous that solid drug delivery systems should be capable of sustained, controlled release of the drug. Further, it is desirable that solid dose delivery systems can be formulated using simple and economical methods.